Sibri Breezhaler - Instructions For Use, Analogues, Price Of Capsules

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Seabree Breezhaler

Sibri Breezhaler: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. In case of impaired renal function
12. 12. For violations of liver function
13. 13. Use in the elderly
14. 14. Drug interactions
15. 15. Analogs
16. 16. Terms and conditions of storage
17. 17. Terms of dispensing from pharmacies
18. 18. Reviews
19. 19. Price in pharmacies

Latin name: Seebri Breezhaler

ATX code: R03BB06

Active ingredient: glycopyrronium bromide (Glycopyrronium bromide)

Producer: Novartis Pharma, AG (Novartis Pharma, AG) (Switzerland)

Description and photo update: 2019-09-07

Prices in pharmacies: from 1672 rubles.

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Sibri Breezhaler is a bronchodilator inhalation drug, m-cholinergic receptor blocker.

Release form and composition

Sibri Breezhaler is produced in the form of capsules with powder for inhalation: size No. 3, solid; the case and the lid are transparent, orange, with a black stripe and the inscription in black ink: on the case - “GPL50” above the black stripe, on the lid there is a marking in the form of the company logo under the black stripe; the contents of the capsules are almost white or white powder [6 or 10 pcs. in a blister, in a cardboard box 1, 2, 3, 4 or 5 blisters, complete with a device for inhalation (Breezhaler); multipack: 15/25 packs of 1 blister, 3 packs of 3/5 blisters or 4 packs of 4 blisters with Breezhaler in a cardboard box, as well as instructions for use of Sibri Breezhaler].

1 capsule contains:

• active substance: glycopyrronium base - 50 μg (equivalent to glycopyrronium bromide in the amount of 63 μg);
• additional substances: magnesium stearate, lactose monohydrate;
• capsule shell: sodium chloride, carrageenan, water, hypromellose, sunset yellow dye; black ink - propylene glycol, shellac, sodium hydroxide, iron dye black oxide.

Pharmacological properties

Pharmacodynamics

Sibri Breezhaler is a long-acting inhalation agent. Glycopyrronium bromide, the active substance of the drug, belongs to m-anticholinergics that block the bronchoconstrictor effect of acetylcholine on the smooth muscle cells of the respiratory tract, which causes a bronchodilating effect. In the human body, 5 types of muscarinic receptors (M _1-5) are found. It was found that only species M _1–3 take part in the physiological function of the respiratory system. Glycopyrronium bromide, which is an antagonist of muscarinic receptors, is characterized by a high affinity mainly for receptors of M _1–3 species. Along with this, the active substance is 4-5 times more sensitive to M ₁ - and M ₃-subtypes of receptors, compared with the M ₂ -subtype. This leads to the rapid development of a therapeutic effect after inhalation of glycopyrronium bromide, which is confirmed by the results of clinical studies.

The duration of action of the drug after inhalation is associated with the long-term maintenance of its therapeutic concentration in the lungs, as evidenced by the longer half-life (T _½) after inhalation use, compared with intravenous (IV) administration. In the course of numerous clinical studies, it was demonstrated that when treating glycopyrronium with bromide in patients with chronic obstructive pulmonary disease (COPD), their pulmonary function significantly improved - the assessment was made by changing the forced expiratory volume in 1 min (FEV ₁).

The therapeutic effect of the active substance is observed within the first 5 minutes after inhalation administration with a significant increase in FEV ₁ from the initial values in the range from 0.091 to 0.094 liters, the bronchodilating effect is observed after inhalation for over 24 hours. According to research data, there was no evidence of the development of tachyphylaxis to the bronchodilating effect of glycopyrronium bromide against the background of its regular use up to 52 weeks. There were also no changes in the heart rate (HR) and the duration of the QTc interval during therapy with Sibri Breezhaler at a dose of 200 μg in patients with COPD.

Pharmacokinetics

After inhalation use, glycopyrronium bromide is intensively absorbed into the systemic circulation, the maximum concentration (C _max) in the blood plasma is observed after 5 minutes, the absolute bioavailability is approximately 40%. Approximately 10% of the total systemic exposure of the agent (AUC) is due to absorption in the gastrointestinal tract (GIT) and 90% to absorption in the lungs.

When administered orally, the absolute bioavailability of glycopyrronium bromide is estimated at 5%. Against the background of regular inhalations once a day, the equilibrium state of the active substance can be achieved within 7 days. In this condition (taking 50 μg once a day) C _{max of} glycopyrronium bromide and its plasma concentration in the blood immediately before the next dose is 166 and 8 pg / ml, respectively. Elimination with urine in a steady state, when compared with the first inhalation, allows us to assume that administration in the dose range of 25-200 mcg does not affect the systemic accumulation of the drug.

After intravenous administration of glycopyrronium bromide, the volume of distribution (V _d) in the equilibrium state (V _ss) and in the terminal phase (V _z) was 83 and 376 liters, respectively. The apparent V _z after inhalation (V _z / F) was 7310 L, which indicates a slower excretion of the agent after inhalation. In in vitro studies, the connection of the active substance with plasma proteins was 38–41% at a level of 1–10 ng / ml. These levels are at least 6 times higher than those in the equilibrium state observed in plasma with the use of the drug once a day, 50 μg.

It was found that as a result of hydroxylation of glycopyrronium bromide, the formation of various mono- and bis-hydroxylated metabolites occurs, and as a result of direct hydrolysis, the formation of carboxylic acid derivatives (M9). In the course of in vitro studies, it was noted that CYP isoenzymes are involved in the oxidative biotransformation of the active substance. It is assumed that hydrolysis to M9 is catalyzed by enzymes from the cholinesterase family. Since in vitro studies did not detect the metabolism of glycopyrronium bromide in the lungs and M9 contributes to an insignificant extent to circulation (4% of C _maxand AUC of the active substance) after intravenous administration, it is believed that M9 is formed from the fraction of the substance absorbed from the gastrointestinal tract (after inhalation) by means of presystemic hydrolysis and / or during the primary passage through the liver. After i.v. or inhalation, only a minimal amount of M9 was detected in urine (less than 0.5% of the initial dose).

During repeated inhalations, glucuronic conjugates and / or glycopyrronium bromide sulfates were detected in urine in an amount of approximately 3% of the dose. An in vitro inhibition study showed that glycopyrronium bromide did not show pronounced activity in inhibiting isoenzymes CYP2A6, CYP1A2, CYP2C9, CYP2C8, CYP2D6, CYP2E1, CYP2C19 or CYP3A4 / 5, transporters MRP2, MXT2, OTR1, OCAT3, transporters OATP1B1 or OATP1B3.

Excretion of the active substance by the kidneys reaches 60–70% of the total plasma clearance, the remaining amount (30–40%) is excreted in the bile or as a result of metabolic transformation. After single and repeated inhalation injections of Sibri Breezhaler 1 time per day in the dose range from 50 to 200 μg to healthy volunteers and patients with COPD, the average renal clearance was in the range of 17.4-24.4 l / h. Active tubular (tubular) secretion promotes the elimination of glycopyrronium bromide by the kidneys, almost 20% of the dose received is detected unchanged in the urine. The concentration of the active substance in the plasma decreases in several phases. Average final T _½is more prolonged after inhalation use (33-57 hours), compared to that after intravenous injection (6.2 hours) and oral administration (2.8 hours). Based on the nature of elimination, it is possible to allow prolonged absorption of glycopyrronium bromide in the lungs and / or its penetration into the systemic circulation for 24 hours or more after inhalation.

Systemic exposure, as well as total urinary elimination of glycopyrronium bromide in equilibrium in patients with COPD, increased in proportion to the dose in the range from 50 to 200 μg.

Population pharmacokinetic analysis of data in patients with COPD found that body weight and age are factors influencing interindividual differences in systemic drug exposure. Sibri Breezhaler at a dose of 50 mcg 1 time per day can be safely used in all age groups and at any body weight.

Systemic exposure to glycopyrronium bromide is largely independent of gender, smoking, and baseline FEV ₁.

Systemic exposure to glycopyrronium bromide is affected by the state of renal function. A moderate increase in AUC up to 1.4 times was noted in the presence of mild / moderate renal impairment and an increase up to 2.2 times in severe or end-stage renal disease.

Patients with impaired liver function did not participate in clinical trials. Since glycopyrronium bromide is eliminated mostly by the kidneys, impairment of its hepatic metabolism is unlikely to cause a clinically significant increase in systemic exposure.

Indications for use

Sibri Breezhaler is indicated for the maintenance therapy of bronchial conduction disorders in patients with COPD.

Contraindications

Absolute:

• age up to 18 years;
• combined use with inhaled drugs, which include other m-anticholinergics;
• glucose-galactose malabsorption, lactase deficiency, galactose intolerance (the product contains lactose);
• hypersensitivity to any of the constituents of Sibri Breezhaler.

Relative (glycopyrronium bromide must be used with caution):

• severe renal failure - glomerular filtration rate (GFR) less than 30 ml / min / 1.73 m², including end-stage renal failure, requiring hemodialysis;
• diseases leading to urinary retention;
• angle-closure glaucoma;
• unstable ischemic heart disease (CHD);
• heart rhythm disturbances;
• lengthening of the QTc interval (QT corrected> 0.44 s);
• a history of myocardial infarction.

Sibri Breezhaler, instructions for use: method and dosage

Sibri Breezhaler is intended for inhalation use only.

Capsules containing powder for inhalation are required to be used only for inhalation through the mouth, produced using a special device for inhalation Breezhaler, included in the package. Powder capsules cannot be taken orally.

Capsules must be stored in a blister and removed from it only immediately before use.

The recommended dose of the drug is 50 mcg (contents of one capsule), administered by inhalation 1 time per day, daily at the same time. If the next inhalation was missed, the next dose should be administered as soon as possible. To compensate for the missed dose, 2 inhalations cannot be carried out, the daily dose of Sibri Breezhaler should not exceed 50 mcg.

If there is no improvement in respiratory function, the doctor needs to make sure that the drug is being used correctly by the patient.

The bronchodilator should be inhaled, not swallowed.

For inhalation of capsules, only Breezhaler must be used, the latter, in turn, cannot be used for inhalation of other means. Throw away the inhaler 30 days after starting use.

How to use the inhaler:

1. After removing the cap, open the Breezhaler inhaler by firmly holding its base and tilting the mouthpiece.
2. Separate 1 capsule from the blister pack along the perforation line. Free it from the protective film and carefully remove it (do not squeeze the capsule through the film).
3. Take out the capsule just before inhalation. Remove the capsule from the blister with dry hands; do not swallow the capsule.
4. Place the capsule in the inhaler, in the capsule chamber, you cannot put it directly into the mouthpiece.
5. Close the inhaler tightly; when it is completely closed, a click should be heard.
6. Hold the inhaler upright with the mouthpiece pointing up. Pierce the capsule by pressing both buttons firmly at the same time. At the moment of piercing the capsule, a click should occur. Press the buttons to pierce the capsule only once.
7. Release buttons on both sides completely.
8. Exhale completely before inserting the mouthpiece into your mouth, but do not blow into the mouthpiece.
9. Holding the inhaler so that the buttons are located on the left and right (and not on the top and bottom), place the mouthpiece in your mouth and wrap your lips tightly around it. Take the medicine by inhaling quickly, evenly, as deeply as possible, without pressing the side buttons.
10. Make sure that when inhaled through the inhaler there is a characteristic rattling sound produced during the rotation of the capsule in the chamber and spraying the powder; there may also be a sweetish taste of the product in the mouth. If the capsule is jammed in the inhaler chamber, there may be no rattling sound. In this case, you need to open the inhaler and carefully release the capsule by knocking on its base. Do not press the side buttons to pierce the capsule. It is recommended to repeat steps 8 and 9 if necessary.
11. If a characteristic sound is heard during the procedure, you need to hold your breath as long as possible (as far as possible, without experiencing unpleasant sensations) and at the same time remove the mouthpiece from your mouth; then exhale. Open the inhaler and check the capsule for powder residue. If there is still powder in the capsule, close the Breezhaler and repeat steps 8-11. Most patients can empty the capsule in 1 or 2 inhalations. In some cases, after inhalation, a cough is noted for a short period, which is not an alarming sign. If there is no powder in the capsule, then the full dose has been taken.
12. After inhalation, remove the empty capsule by tilting the mouthpiece and knocking on the inhaler, and then discard it. Close the mouthpiece and close the Breezhaler cap. Do not store capsules in the inhaler.

You should never blow into the mouthpiece of the inhaler. Store blisters with capsules and inhaler in a dry place. If you need to use capsules from a new package, you must always use the new inhaler in the package to inhale them.

In extremely rare cases, a small volume of capsule contents may enter the mouth. When inhaling or swallowing the Seabri Breezhaler, don't worry.

It must be remembered that when the capsule is pierced more than once, the risk of breakage increases.

It is recommended to clean the inhalation device once a week. The mouthpiece should be wiped inside and out with a dry cloth. You cannot use water to clean the inhaler; it must be kept dry.

Side effects

The frequency of occurrence of undesirable reactions of Sibri Breezhaler is estimated according to the following criteria: often - from> 1/100 to 1/1000 to <1/100:

• metabolism and nutritional disorders: infrequently - hyperglycemia;
• infectious and parasitic diseases: often - nasopharyngitis; infrequently - cystitis, rhinitis;
• nervous system and psyche: often - headache, insomnia; infrequently - hypesthesia;
• respiratory system, organs of the chest and mediastinum: infrequently - irritation of the pharynx, congestion in the paranasal sinuses, epistaxis, productive cough;
• heart: infrequently - palpitations, atrial fibrillation;
• skin and subcutaneous tissue: infrequently - skin rash;
• digestive system: often - dryness of the oral mucosa, gastroenteritis; infrequently - dental caries, dyspepsia;
• kidneys and urinary tract: often - urinary tract infection; infrequently - urinary retention, dysuria;
• musculoskeletal and connective tissue: infrequently - musculoskeletal pain in the chest area, pain in the limbs;
• general disorders: infrequently - asthenia, fatigue.

In a clinical study lasting 12 months, the following additional undesirable effects were found, which were more common with the use of Sibri Breezhaler, compared with placebo: vomiting, nasopharyngitis, neck pain, muscle pain, diabetes mellitus.

Violations recorded during post-registration studies and according to literature data:

• organs of the chest and mediastinum: paradoxical bronchospasm;
• skin and subcutaneous tissues: itchy skin;
• immune system: hypersensitivity, angioedema.

In patients over 75 years of age, the incidence of headache and urinary tract infections with the use of Sibri Breezhaler was higher than in the placebo group.

Overdose

The use of glycopyrronium in high doses may cause the development of symptoms associated with m-anticholinergic activity, and require appropriate symptomatic treatment.

In patients with COPD, regular inhalation of Sibri Breezhaler in a total dose of 100 and 200 mcg 1 time per day for 28 days was well tolerated. In blood plasma after intravenous administration of glycopyrronium bromide at a dose of 150 μg (equivalent to glycopyrronium at a dose of 120 μg), C _max and AUC of the drug in healthy volunteers were approximately 50 and 6 times higher, respectively, than C _max in blood plasma and AUC in equilibrium. condition noted when using Sibri Breezhaler inhalation at a dose of 50 mcg 1 time per day. Overdose symptoms in this case were not detected.

Acute intoxication due to accidental oral intake of capsules is unlikely due to the low bioavailability of glycopyrronium bromide when taken orally (about 5%).

special instructions

Sibri Breezhaler is not intended for the relief of acute episodes of bronchospasm.

After using the drug, cases of immediate hypersensitivity reactions were recorded. If signs appear indicating the development of an allergic reaction, including skin rash, urticaria, angioedema (difficulty swallowing or breathing, swelling of the lips, tongue and face), you must immediately stop using Sibri Breezhaler and choose an alternative therapy.

Against the background of drug treatment, as well as during other inhalation therapy, the development of paradoxical bronchospasm, which is a threat to life, can be observed. If this complication occurs, it is required to immediately stop using the drug and start alternative therapy.

It is also necessary to urgently cancel the inhalation agent and consult a doctor if any sign or symptom of acute angle-closure glaucoma develops.

Sibri Breezhaler capsules are recommended for the maintenance treatment of patients with COPD. Since the general population of COPD is significantly dominated by patients over 40 years old, when using the drug in patients under 40 years old, confirmation of the diagnosis of COPD using spirometry is necessary.

Influence on the ability to drive vehicles and complex mechanisms

Seabri Breezhaler does not adversely affect the ability to drive vehicles and other moving complex machinery.

Application during pregnancy and lactation

In the process of preclinical studies, no teratogenic effect was recorded after inhalation of Siberri Breezhaler capsules. Since there are no data on its use in pregnant women, prescribing the drug during pregnancy is possible only if the intended benefit of therapy for the patient significantly outweighs the possible threat to the fetus.

It is not known whether glycopyrronium bromide is excreted in human milk in humans, therefore, the use of Sibri Breezhaler during breastfeeding can be considered only if the benefits of taking it to the woman outweigh any likely risk to the infant.

Animal studies, including data from reproductive toxicity studies, do not suggest that the drug may affect fertility in women or men.

Pediatric use

Reception of Sibri Breezhaler is contraindicated in patients under the age of 18.

With impaired renal function

In patients with COPD and functional renal impairment of mild / moderate severity (GFR ≥ 30 ml / min / 1.73 m²), Sibri Breezhaler can be used in recommended doses.

In the presence of severe renal impairment (GFR <30 ml / min / 1.73 m²) or end-stage kidney disease requiring hemodialysis treatment, the drug can be used at the recommended dose only when the expected benefit from taking it significantly outweighs the potential risk. Patients from this risk group should be closely monitored in order to timely identify the occurrence of possible undesirable effects.

For violations of liver function

In the presence of functional disorders of the liver, Sibri Breezhaler should be used at the recommended dose.

Use in the elderly

Elderly patients do not need dose adjustment of Sibri Breezhaler.

Drug interactions

• other medicinal products for inhalation use containing m-anticholinergics: these interactions have not been studied, and therefore the combined use of these agents with glycopyrronium bromide is contraindicated;
• indacaterol, β ₂ -adrenergic receptor agonist (for inhalation use): no effect on the pharmacokinetics of this substance and glycopyrronium bromide was observed;
• drugs widely used for the treatment of COPD, including methylxanthines, beta-adrenomimetics, glucocorticosteroids for oral and inhalation use: no clinically significant manifestations of drug interactions were recorded when Sibri Breezhaler was combined with these drugs in clinical practice;
• cimetidine and other inhibitors of organic cation transporters that affect the renal clearance of glycopyrronium bromide: in healthy volunteers during clinical studies, the AUC of glycopyrronium bromide increased by 22% and renal clearance decreased by 23% when used concomitantly with cimetidine; when the drug is combined with these substances, no clinically significant interaction is expected.

According to in vitro studies, Sibri Breezhaler is not expected to affect the metabolism of other drugs.

Inhibition / induction of metabolic transformation of glycopyrronium bromide does not cause significant changes in systemic exposure of the drug.

Analogs

The counterpart of Seabree Breezhaler is Ultibro Breezhaler.

Terms and conditions of storage

Store in original packaging at a temperature not exceeding 25 ° C.

Shelf life is 2 years.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews of Seabree Breezhaler

The few reviews about Seabree Breezhaler are mostly positive. Patients with COPD, who have been using this bronchodilator for a long time as a maintenance therapy, note that it promotes easier and deeper breathing, prevents the development of attacks of suffocation at night, and significantly improves the general condition.

All patients attribute its high cost to the disadvantages of Sibri Breezhaler, there are no complaints about the appearance of undesirable reactions.

Price for Sibri Breezhaler in pharmacies

The price of Seabree Breezhaler for a package containing 30 capsules with powder for inhalation and a device for inhalation Breezhaler can be 1450-1900 rubles.

Seabree Breezhaler: prices in online pharmacies

Drug name Price Pharmacy

Sibri Breezhaler 50 mcg capsules with powder for inhalation complete with Breezhaler inhaler 30 pcs. 1672 RUB Buy

Sibri Breezhaler capsules for inhalation. 50μg 30 pcs. 1918 RUB Buy

Maria Kulkes Medical journalist About the author

Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!